Certain antibiotics which are active against a broad range of Gram-positive and other bacteria are known to be produced by species of microorganisms isolated from soil samples throughout the world. There is an ongoing need, however, for new antimicrobial agents which show improved activity, have an improved or specific spectrum of efficacy, and/or exhibit more desirable pharmacokinetic properties when administered to a patient. One avenue of research has involved the derivatization of antibiotics in an effort to improve their antimicrobial properties.
In the case of antibacterial-associated or other nosocomial colitis, there is a particular need for antimicrobial agents which offer an improvement in long-term cure rate, i.e., which reduce the incidence of relapse often seen with commonly-used drugs such as vancomycin or metronidazole. Antibiotic-associated colitis, which can arise when normal gastrointestinal flora have been suppressed by antibiotic therapy, is often caused by the organism Clostridium difficile. It is therefore an aim of the present invention to provide antimicrobial agents which are particularly active against Clostridium while still permitting the re-establishment of some or all of the normal flora.